This grant application requests funds for the purchase of an FEI Technai G2 Spirit Bio- Twin transmission electron microscope. This essential instrument is needed to replace an aged and undependable >30 year old Philips 400 TEM in the sole shared-use microscopy core facility in the Wake Forest University School of Medicine. This new instrument has computer-controlled operating systems, a digital imaging camera, and up to 120kV accelerating voltage to allow high resolution TEM imaging of biological specimens. Space, administration, highly-experienced technicians and institutional support for this shared microscopy core have been in place for over 20 years, and support the research of several NIH grant-funded investigators in many different departments, including a group of 10 investigators listed in this application as current major users. The core facility includes, in addition to the TEM instrument, an existing SEM instrument and light-based microscopy instruments, including digital fluorescence, confocal, time-lapse and laser-capture microdissection microscopes, all of which serve as strong correlative tools for the analysis of TEM samples. The core provides TEM support preparative services, including embedding and thin sectioning, cryoultramicrotomy, fixed angle and rotary shadowing and negative staining, as well as immunocytochemical techniques. The acquisition of this new microscope is critical to provide a state-of-the art instrument to continue the support of microscopy needs for NIH-funded investigators, with improved flexibility and dependability for these and for new research projects.